The Inhibition of Aldose Reductase Accelerates Liver Regeneration through Regulating Energy Metabolism
| Autor: | Wang Jie Jiang, Gao Chao Li, Chen Huan Luo, Xiangcheng Li, Chang Xian Li, Hong Wei Wang, Yao Dong Zhang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Aging medicine.medical_specialty Article Subject medicine.medical_treatment Liver transplantation Biochemistry Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Adenosine Triphosphate Aldehyde Reductase Internal medicine Cyclins medicine Animals Hepatectomy Enzyme Inhibitors Aldose reductase Organelle Biogenesis QH573-671 Chemistry Regeneration (biology) Fatty liver Body Weight Cell Biology General Medicine Organ Size medicine.disease Liver regeneration Liver Regeneration Up-Regulation Fatty Liver Mice Inbred C57BL Disease Models Animal 030104 developmental biology Endocrinology Mitochondrial biogenesis Liver 030220 oncology & carcinogenesis Reperfusion Injury Knockout mouse Cytology Energy Metabolism Research Article |
| Zdroj: | Oxidative Medicine and Cellular Longevity Oxidative Medicine and Cellular Longevity, Vol 2020 (2020) |
| ISSN: | 1942-0900 |
| DOI: | 10.1155/2020/3076131 |
| Popis: | Objectives. Our previous study showed that aldose reductase (AR) played key roles in fatty liver ischemia-reperfusion (IR) injury by regulating inflammatory response and energy metabolism. Here, we aim to investigate the role and mechanism of AR in the regeneration of normal and fatty livers after liver surgery. Methods. The association of AR expression with liver regeneration was studied in the rat small-for-size liver transplantation model and the mice major hepatectomy and hepatic IR injury model with or without fatty change. The direct role and mechanism of AR in liver regeneration was explored in the AR knockout mouse model. Results. Delayed regeneration was detected in fatty liver after liver surgery in both rat and mouse models. Furthermore, the expression of AR was increased in liver after liver surgery, especially in fatty liver. In a functional study, the knockout of AR promoted liver regeneration at day 2 after major hepatectomy and IR injury. Compared to wild-type groups, the expressions of cyclins were increased in normal and fatty livers of AR knockout mice. AR inhibition increased the expressions of PPAR-α and PPAR-γ in both normal liver and fatty liver groups after major hepatectomy and IR injury. In addition, the knockout of AR promoted the expressions of SDHB, AMPK, SIRT1, and PGC1-α in liver, which regulated mitochondrial biogenesis and energy metabolism. Conclusions. The knockout of AR promoted the regeneration of normal and fatty livers through regulating energy metabolism. AR may be a new potential therapeutic target to accelerate liver regeneration after surgery. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text